Pleiotropic function of TRPV4 ion channels in the central nervous system

NEW FINDINGS: What is the topic of this review? In this concise review, we highlight insights into the role of transient receptor potential, vanilloid type 4 (TRPV4) ion channels in the CNS, results that have been contributed over the last 16 years since the initial discovery of the channel. What advances does it highlight? TRPV4 has been found to function in neurons, astroglia and microglia, both in physiological (e.g. astrocytic neurovascular coupling, neuronal membrane potential at physiological temperature) and in pathological conditions (e.g. mechanical trauma), so far recorded as exciting findings in need of more in-depth mechanistic clarification. Transient receptor potential, vanilloid type 4 (TRPV4) ion channels are osmo-mechano-TRP channels, with pleiotropic function and expression in many different types of tissues and cells. They have also been found to be involved in pain and inflammation. Studies have focused on the role of TRPV4 in peripheral sensory neurons, but its expression and function in central nervous glial cells and neurons has also been documented. In this overview, based on the senior author's (WL) lecture at the recent recent joint meeting of APS/The Physiological Society in Dublin, we concisely review evidence of TRPV4 expression and function in the CNS and how TRPV4 function can be modulated for therapeutic benefit of neuropsychiatric disorders. Novel TRPV4-inhibitory compounds developed recently in the authors' laboratory are also discussed.